Papiernik M, Pontoux C, Golstein P
U.345 INSERM, Institut Necker, Paris, France.
Eur J Immunol. 1995 Jun;25(6):1517-23. doi: 10.1002/eji.1830250607.
To investigate the role of Fas in the induction of tolerance by viral superantigen (SAG), we infected MRL-+/+ and MRL-lpr (Fas mutant) mice with mouse mammary tumor virus (MMTV) (SW), a virus encoding an SAG with the same specificity as endogenous Mtv-7-SAG. In normal mice, this infection has two distinct consequences on specific V beta 6+CD4+ T cells, consisting of activation followed by clonal deletion. MMTV (SW)-SAG-induced activation in vivo was identical in MRL-+/+ and MRL-lpr mice. In contrast, clonal deletion showed age-dependent impairment. Early infection (5 weeks) led to identical clonal deletion of specific T cells in blood lymphocytes from MRL-+/+ and MRL-lpr mice, although clonal deletion was slightly impaired in the MRL-lpr lymph nodes. Late infection (10 weeks) of MRL-lpr mice led to markedly delayed and reduced clonal deletion. V beta 6+CD4+ T cells which escaped clonal deletion in aging MRL-lpr mice were not anergized by interaction with SAG. These results show that peripheral clonal deletion induced by viral SAG in adult mice is controlled by Fas, but not exclusively so.
为了研究Fas在病毒超抗原（SAG）诱导的免疫耐受中的作用，我们用小鼠乳腺肿瘤病毒（MMTV）（SW）感染了MRL-+/+和MRL-lpr（Fas突变）小鼠，该病毒编码一种与内源性Mtv-7-SAG具有相同特异性的SAG。在正常小鼠中，这种感染对特定的Vβ6+CD4+T细胞有两个不同的影响，包括激活后克隆性缺失。MMTV（SW）-SAG在体内诱导的激活在MRL-+/+和MRL-lpr小鼠中是相同的。相反，克隆性缺失表现出年龄依赖性损伤。早期感染（5周）导致MRL-+/+和MRL-lpr小鼠血液淋巴细胞中特定T细胞的克隆性缺失相同，尽管MRL-lpr淋巴结中的克隆性缺失略有受损。MRL-lpr小鼠的晚期感染（10周）导致克隆性缺失明显延迟和减少。在衰老的MRL-lpr小鼠中逃脱克隆性缺失的Vβ6+CD4+T细胞不会因与SAG相互作用而失能。这些结果表明，成年小鼠中病毒SAG诱导的外周克隆性缺失受Fas控制，但并非完全如此。
